Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.
Seyedehsadaf AsfaHalil Ibrahim ToyReza Arshinchi BonabGeorge P ChrousosAthanasia PavlopoulouStyliani A GeronikolouPublished in: International journal of environmental research and public health (2023)
Ewing sarcoma is a rare type of cancer that develops in the bones and soft tissues. Drug therapy represents an extensively used modality for the treatment of sarcomas. However, cancer cells tend to develop resistance to antineoplastic agents, thereby posing a major barrier in treatment effectiveness. Thus, there is a need to uncover the molecular mechanisms underlying chemoresistance in sarcomas and, hence, to enhance the anticancer treatment outcome. In this study, a differential gene expression analysis was conducted on high-throughput transcriptomic data of chemoresistant versus chemoresponsive Ewing sarcoma cells. By applying functional enrichment analysis and protein-protein interactions on the differentially expressed genes and their corresponding products, we uncovered genes with a hub role in drug resistance. Granted that non-coding RNA epigenetic regulators play a pivotal role in chemotherapy by targeting genes associated with drug response, we investigated the non-coding RNA molecules that potentially regulate the expression of the detected chemoresistance genes. Of particular importance, some chemoresistance-relevant genes were associated with the autonomic nervous system, suggesting the involvement of the latter in the drug response. The findings of this study could be taken into consideration in the clinical setting for the accurate assessment of drug response in sarcoma patients and the application of tailored therapeutic strategies.
Keyphrases
- genome wide identification
- genome wide
- bioinformatics analysis
- high throughput
- single cell
- transcription factor
- end stage renal disease
- gene expression
- adverse drug
- soft tissue
- poor prognosis
- randomized controlled trial
- high grade
- systematic review
- genome wide analysis
- newly diagnosed
- induced apoptosis
- multidrug resistant
- high resolution
- heart rate variability
- prognostic factors
- drug induced
- mesenchymal stem cells
- papillary thyroid
- rna seq
- young adults
- cell death
- peritoneal dialysis
- blood pressure
- deep learning
- nucleic acid
- lymph node metastasis
- pi k akt